UF scientists offer clinical science view of exploring the potential of brain-derived adult stem cells
GAINESVILLE, Fla. — Adult stem cell research holds great promise for treating some neurological disorders, but much work remains before laboratory efforts can be translated into safe treatments, two University of Florida researchers write in a position paper in Saturday’s issue of The Lancet.
The capability and flexibility of stem cells derived from adults have been questioned when compared to their younger embryonic counterparts, but scientists are discovering that older cells have potential if treated the right way. The use of adult stem cells also offers an avenue to bypass the controversy linked to embryonic stem cells derived from aborted fetuses or embryos created for fertility treatments.
“This has become a very politically, religiously, morally, economically and scientifically charged area, and there is a tremendous amount written on the subject in reviews and summaries and new research, but not much has been written about where this is all going and what we should focus on,” said pediatric neurosurgeon Dr. David W. Pincus, who co-authored The Lancet article with Dennis A. Steindler, a professor of neuroscience. Both Pincus and Steindler are affiliated with the Evelyn F. and William L. McKnight Brain Institute of UF.
Pincus said there are three important things to remember regarding adult stem cell research: 1) People should not be afraid of this technology; 2) it is going to be a very important technology for helping to heal diseases, including those of the nervous system; and 3) it will not cure everything.
UF researchers hope to conduct clinical trials for a variety of neurological disorders in the next five years. Scientists around the world are exploring the use of adult neural stem cell treatment techniques for various conditions, including stroke, brain tumors, Alzheimer’s disease, brain injury and birth-related neurological injuries. Neurological disorders strike an estimated 50 million Americans each year, according to the National Institute of Neurological Disorders and Stroke.
With differing viewpoints regarding the potential impact of adult neural stem cells and whether they have the same potential usefulness as embryonic stem cells, scientists now are looking into comparative studies to determine the benefits of each type of stem cell.
Steindler and Pincus focus on the concept of self-repair, in which a person’s own cells are used in treatment methods. Previously believed to remain relatively inactive after birth, brain stem cells have been shown to regenerate and can be stimulated to reproduce. This self-repair approach, for example, could have the potential for using stem cells from a person’s own healthy brain tissue to replace tissue damaged by disease. They cite other tissue-specific stem cells, such as those found in the liver and pancreas, which also can be enticed to grow.
Another possible method is converting cells from other parts of the body that are in a mode of repair, such as those derived from bone marrow, into neural cells and use them in the self-repair process.
“The bottom line is that we think the ideal strategy is to use a patient’s own cells,” Pincus said. “Precursors can be harvested from brain, blood, bone marrow or skin, and then manipulated into the desired cell for replacement.”
Alternatively, gaining an understanding of the mechanisms in normal development that control stem cell differentiation and growth, and how they can be manipulated to do what is deficient in a patient’s body, could help to eliminate the need for harvesting and transplanting cells, he added.
Although tissue-specific cells are able to give rise to other tissues, such as brain to blood, blood to brain, and brain to muscle, it is possible that they may not possess all of the characteristics of the cell into which they have been transformed. This area of research needs further exploration.
Researchers also have shown that certain adult neural cells, created to perform the specific functions of the central nervous system, can be de-differentiated and thus revert back to a less mature phase, which can then be coaxed (re-differentiated) into cells that perform other specific functions.
“If we can de-differentiate an old cell into a stem cell, we would have an unlimited possibility of what we can do,” said Steindler, who is part of a multidisciplinary stem cell team at UF. “We can take old brain cells, turn them into stem cells and then have them repair the brain of the individual from whom they have been harvested.”
In The Lancet article, Pincus and Steindler outline future directions of study that are necessary before research findings can be applied to patient care. These include additional study on the mechanisms of de-differentiating cells and turning one kind of cell into another tissue-specific cell; developing better ways to isolate and purify adult stem cells to ensure high quality; investigating the apparent innate ability of stem cells from the hippocampus and subependymal zone, in the forebrain, to reproduce and migrate to injured areas of the central nervous system; and evaluating (in both living and test tube models of cell replacement) how the cell’s offspring will integrate into existing circuits.
As researchers begin to manipulate cells, such as turning blood cells into brain cells, Steindler said, they need to learn to control growth so that inappropriate abnormal tissue such as tumors do not occur. He added that in the near future it may be best to restrict this practice to healthy cells taken from the diseased or injured organ until there is a better understanding of how to control cells after the transformation process.
For safety considerations, a greater understanding of the biology of adult stem cells and studies in standardized models to evaluate efficacy are necessary before research outcomes can be translated into therapies for disease, the authors said.
In a recent issue of Nature, another group of UF stem cell program scientists, headed by Dr. Naohiro Terada, an associate professor of pathology, immunology and laboratory medicine, said research showing adult stem cells, such as bone marrow, turning into other types of tissues will need to be looked at more closely because it may be that the stem cells are actually fusing with existing cells, not transforming into a new type of cell. Both the Terada, and Steindler and Pincus papers, along with a new study to be published soon by the Steindler lab, raise the need for more experimental studies of any stem cell population before allowing them to be applied in human medicine. None of these studies, however, undercuts the potential value these cells will have in the new field of regeneration medicine, according to Steindler.